Radiofrequency ablation versus repeat resection for recurrent hepatocellular carcinoma (≤ 5 cm) after initial curative resection

Abstract

Objectives

Recurrence rate is up to 70% at 5 years for hepatocellular carcinoma (HCC) after initial resection, but the management of recurrent HCC remains unclear. To compare the efficacy and safety of radiofrequency ablation (RFA) and repeat resection as the first-line treatment in recurrent HCC.

Methods

This multicenter retrospective study analyzed 290 patients who underwent RFA (n = 199) or repeat resection (n = 91) between January 2006 and December 2016 for locally recurrent HCC (≤ 5 cm) following primary resection. We compared the overall survival (OS), progression-free survival (PFS), and complications between the two treatment groups for the total cohort and the propensity score matched (PSM) cohort.

Results

The 1-, 3-, and 5-year OS (90.7%, 69.04%, 55.6% vs. 87.7%, 62.9%, 38.1%, p = 0.11) and PFS (56.5%, 27.9%, 14.6% vs. 50.2%, 21.9%, 19.2%, p = 0.80) were similar in the RFA group and the repeat resection group. However, RFA was superior to repeat resection in complication rate and hospital stay (p ≤ 0.001). We observed similar findings in the PSM cohort of 48 pairs of patients and when OS and PFS were measured from the time of the primary resection. The OS of the RFA group was significantly better than repeat resection group among those with 2 or 3 recurrent tumor nodules in both the total cohort (p = 0.009) and the PSM cohort (p = 0.018).

Conclusion

RFA has the same efficacy as repeat resection in recurrent HCC patients, but with fewer complications. RFA is more efficient and safer than repeat resection in patients with 2 or 3 recurrent tumor nodules.

Key Points

• Recurrence rate is up to 70% at 5 years for hepatocellular carcinoma (HCC) after initial resection.

• RFA has the same efficacy as repeat resection in recurrent HCC patients, but with fewer complications.

• RFA may be preferred for those with 2 or 3 recurrent HCC nodules.

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Abbreviations

ALT:

Alanine aminotransferase

CI:

Confidence interval

HCC:

Hepatocellular carcinoma

HR:

Hazard ratio

MELD:

Model for end-stage liver disease

MRI:

Magnetic resonance imaging

OS:

Overall survival

PFS:

Progression-free survival

PSM:

Propensity score matching

RFA:

Radiofrequency ablation

References

  1. 1.

    Marrero JA, Kulik LM, Sirlin CB et al (2018) Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 68:723–750

    Article  Google Scholar 

  2. 2.

    Hasegawa K, Kokudo N, Makuuchi M et al (2013) Comparison of resection and ablation for hepatocellular carcinoma: a cohort study based on a Japanese nationwide survey. J Hepatol 58:724–729

    Article  Google Scholar 

  3. 3.

    Chan AWH, Zhong J, Berhane S et al (2018) Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection. J Hepatol 69:1284–1293

    Article  Google Scholar 

  4. 4.

    Tabrizian P, Jibara G, Shrager B, Schwartz M, Roayaie S (2014) Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg 261:947–955

    Article  Google Scholar 

  5. 5.

    Poon RT, Fan ST, Lo CM, Liu CL, Wong J (2002) Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function. Implication for a strategy of salvage transplantation. Ann Surg 235:373–382

  6. 6.

    Xu XF, Xing H, Han J et al (2018) Risk factors, patterns, and outcomes of late recurrence after liver resection for hepatocellular carcinoma: a multicenter study from China. JAMA Surg 154:209–217

    Article  Google Scholar 

  7. 7.

    Lacaze L, Scotté M (2015) Surgical treatment of intra hepatic recurrence of hepatocellular carcinoma. World J Hepatol 116:1755–1760

    Article  Google Scholar 

  8. 8.

    Ma KW, Chok KSH, She BWH et al (2017) Defining optimal surgical treatment for recurrent hepatocellular carcinoma. -a propensity score matched analysis. Liver Transpl 24:1062–1069

    Article  Google Scholar 

  9. 9.

    Peng SK, Chan ACY, Tan TC et al (2016) Efficacy of radiofrequency ablation compared with transarterial chemoembolization for the treatment of recurrent hepatocellular carcinoma: a comparative survival analysis. HPB (Oxford) 18:72–78

  10. 10.

    Yagi R, Midorikawa Y, Moriguchi M et al (2018) Liver resection for recurrent hepatocellular carcinoma to improve survivability: a proposal of indication criteria. Surgery 163:1250–1256

    Article  Google Scholar 

  11. 11.

    European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69:182–236

  12. 12.

    Chu HH, Kim JH, Kim PN et al (2019) Surgical resection versus radiofrequency ablation very early-stage HCC (≤ 2 cm single HCC): a propensity score analysis. Liver Int 39:2397–2407

    Article  Google Scholar 

  13. 13.

    Liu H, Wang ZG, Fu SY et al (2016) Randomized clinical trial of chemoembolization plus radiofrequency ablation versus partial hepatectomy for hepatocellular carcinoma within the Milan criteria. Br J Surg 103:348–356

    CAS  Article  Google Scholar 

  14. 14.

    Kyoung Doo S, Hyo Keun L, Hyunchul R et al (2015) Repeated hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma after hepatic resection: a propensity score matching study. Radiology 275:599–608

    Article  Google Scholar 

  15. 15.

    Peng Z, Wei M, Chen S et al (2018) Combined transcatheter arterial chemoembolization and radiofrequency ablation versus hepatectomy for recurrent hepatocellular carcinoma after initial surgery: a propensity score matching study. Eur Radiol 28:3522–3531

    Article  Google Scholar 

  16. 16.

    Takayama T, Sekine T, Makuuchi M et al (2000) Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet 356:802–807

    CAS  Article  Google Scholar 

  17. 17.

    Kang TW, Lim HK, Lee MW, Kim YS, Choi D, Rhim H (2014) Perivascular versus nonperivascular small HCC treated with percutaneous RF ablation: retrospective comparison of long-term therapeutic outcomes. Radiology 270:888–899

    Article  Google Scholar 

  18. 18.

    Lee S, Kang TW, Dong IC et al (2018) Radiofrequency ablation versus surgery for perivascular hepatocellular carcinoma: propensity score analyses of long-term outcomes. J Hepatol 69:70–78

    Article  Google Scholar 

  19. 19.

    Kang TW, Lim HK, Lee MW, Kim YS, Choi D, Rhim H (2013) First-line radiofrequency ablation with or without artificial ascites for hepatocellular carcinomas in a subcapsular location: local control rate and risk of peritoneal seeding at long-term follow-up. Clin Radiol 68:e641–e651

    CAS  Article  Google Scholar 

  20. 20.

    Kim YJ, Raman SS, Yu NC, Busuttil RW, Tong M, Lu DS (2008) Radiofrequency ablation of hepatocellular carcinoma: can subcapsular tumors be safely ablated? AJR Am J Roentgenol 190:1029–1034

    Article  Google Scholar 

  21. 21.

    Feng YM, Xing W, Le W et al (2017) Efficacy and safety of combination therapy of chemoembolization and radiofrequency ablation with different time intervals for hepatocellular carcinoma patients. Surg Oncol 26:236–241

    Article  Google Scholar 

  22. 22.

    Kang TW, Kim JM, Rhim H et al (2015) Small hepatocellular carcinoma: radiofrequency ablation versus nonanatomic resection--propensity score analyses of long-term outcomes. Radiology 275:908–919

    Article  Google Scholar 

  23. 23.

    Chen MS, Li JQ, Zheng Y et al (2006) A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 243:321–328

    Article  Google Scholar 

  24. 24.

    Xia Y, Li J, Liu G et al (2019) Long-term effects of repeat hepatectomy vs percutaneous radiofrequency ablation among patients with recurrent hepatocellular carcinoma: a randomized clinical trial. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2019.4477

  25. 25.

    Sun WC, Chen I, Liang HL et al (2017) Comparison of repeated surgical resection and radiofrequency ablation for small recurrent hepatocellular carcinoma after primary resection. Oncotarget 8:104571–104581

    Article  Google Scholar 

  26. 26.

    Feng Q, Chi Y, Liu Y, Zhang L, Liu Q (2015) Efficacy and safety of percutaneous radiofrequency ablation versus surgical resection for small hepatocellular carcinoma: a meta-analysis of 23 studies. J Cancer Res Clin Oncol 141:1–9

    Article  Google Scholar 

  27. 27.

    Fu C, Liu N, Deng Q, Li X, Ma K, Bie P (2014) Radiofrequency ablation vs. surgical resection on the treatment of patients with small hepatocellular carcinoma: a system review and meta-analysis of five randomized controlled trials. Hepato-gastroenterology 61:1722–1729

    Google Scholar 

  28. 28.

    Zhao C, Jin M, Le RH et al (2018) Poor adherence to hepatocellular carcinoma surveillance: a systematic review and meta-analysis of a complex issue. Liver Int 38:503–514

    Article  Google Scholar 

  29. 29.

    Wang C, Zhao C, Le AK et al (2015) 729 Poor adherence and poor persistency of consistent adherence to AASLD guidelines for hepatocellular carcinoma (HCC) screening and surveillance in chronic hepatitis B (CHB) patients at both university and community clinics: a multicenter U.S. cohort stud. Gastroenterology 148:S992–S993

    Article  Google Scholar 

  30. 30.

    Feng K, Yan J, Li X et al (2012) A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol 57:794–802

    Article  Google Scholar 

  31. 31.

    Wang JH, Wang CC, Hung CH, Chen CL, Lu SN (2012) Survival comparison between surgical resection and radiofrequency ablation for patients in BCLC very early/early stage hepatocellular carcinoma. J Hepatol 56:412–418

    Article  Google Scholar 

  32. 32.

    Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:052–060

    CAS  Article  Google Scholar 

  33. 33.

    Kaibori M, Matsui Y, Hijikawa T, Uchida Y, Kwon AH, Kamiyama Y (2006) Comparison of limited and anatomic hepatic resection for hepatocellular carcinoma with hepatitis C. Surgery 139:385–394

    Article  Google Scholar 

  34. 34.

    Zhao Y, Wang WJ, Guan S et al (2013) Sorafenib combined with transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma: a large-scale multicenter study of 222 patients. Ann Oncol 24:1786–1792

    CAS  Article  Google Scholar 

  35. 35.

    Chen VL, Yeh ML, Le AK et al (2018) Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience. Aliment Pharmacol Ther 48:44–54

    CAS  Article  Google Scholar 

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Acknowledgments

The authors would like to thank Prof. Ying Zhang (Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States) for the revision of the draft.

Funding

This work was supported in part by the National Natural Science Foundation of China (No. 81570551; 81770607) and Key Research Project of Shandong Province (No. 2016GSF201008).

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Correspondence to Qiang Zhu.

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Guarantor

The scientific guarantor of this publication is Prof. Qiang Zhu.

Conflict of interest

Dr. Mindie H. Nguyen has received research support from the National Cancer Institute, B.K. Kee Foundation, Gilead, Pfizer, and has served as consultant and/or advisory board member for Exact Sciences, Laboratory of Advanced Medicine, Gilead, Eisai, Bayer, Spring Bank, and Novartis.

All other authors hereby declare that there is no potential or actual personal, financial, or political interest related to this study.

Statistics and biometry

No complex statistical methods were necessary for this paper.

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Written informed consent was waived by the Institutional Review Board.

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Institutional Review Board approval was obtained.

Methodology

• retrospective

• prognostic study

• multicenter study

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Feng, Y., Wu, H., Huang, D.Q. et al. Radiofrequency ablation versus repeat resection for recurrent hepatocellular carcinoma (≤ 5 cm) after initial curative resection. Eur Radiol (2020). https://doi.org/10.1007/s00330-020-06990-8

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Keywords

  • Hepatocellular carcinoma
  • Radiofrequency ablation
  • Hepatectomy
  • Treatment outcome